A new family of non-toxic, water-soluble, low molecular weight, immunostimulatory, chemical compositions developed by the Theracel Corporation will be assessed for their utility as vaccine adjuvants. The butyrolactones, which include two classes of chemical compositions, the methylfurylbutyrolactones (MFBLs) and ketobutyrolactones (KBLs) are to be tested in animal models. The experimental design will employ commercially prepared alum-free and alum-containing vaccines [diphtheria, tetanus, influenza A & B, HIV-1 (gp-160/120, p24)] in model which compares the new compositions with current adjuvants. The parameters for immune responsiveness will include assays to measure both specific humoral and cell-mediated immunity. Since Theracel's butyrolactones are orally active, the concept of an oral adjuvant will be evaluated in addition to the classical co-administration as a constituent of the vaccine preparation. Emphasis will be placed on selection of the optimum butyrolactone which can augment both humoral and cell-mediated immunity. Successful completion of the phase I SBIR will yield a new adjuvant composition that will produce the broader and more intense immune response needed for newer genetically engineered, synthetic, as well as purified subunit vaccines which are often weakly immunogenic. The new butyrolactone adjuvant may prove useful in combination with new vaccines under development for the prevention of Acquired Immune Deficiency syndrome (AIDS).